Automated embedding machine, and methods for embedding a histological sample

ABSTRACT

An automated embedding machine includes at least a conveyor, a pouring station, and a cooling station. The conveyor is embodied and arranged to receive casting molds each having at least one histological sample arranged therein, and to transport them to the pouring station which fills each casting mold with an embedding medium heated to above its melting point, and then to the cooling station which cools the embedding medium of each casting mold to below its melting point. The disclosure furthermore relates to a method for embedding a histological sample.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a divisional application of U.S. application Ser.No. 14/552,946 filed Nov. 25, 2014, which claims priority of Germanpatent application number 10 2013 225 397.4 filed Dec. 10, 2013, theentire disclosures of which are incorporated by reference herein.

FIELD OF THE INVENTION

The invention relates to an automated embedding machine.

BACKGROUND OF THE INVENTION

The manner in which a biological tissue sample is to be prepared forhistological investigation is known. Firstly the tissue sample is cut tosize and introduced into a cassette. The sample is then prepared, usinga plurality of chemical treatments, for microscopic investigation. Inthe context of chemical treatment, firstly the sample is fixed with afixing medium, the water present in the sample is removed, andoptionally further processing steps are completed. At the end of thismulti-step process is infiltration of an infiltration medium, usuallyparaffin, into the sample. The sample is then embedded, usuallymanually, into an embedding medium, usually paraffin, by means of amolding operation, and the embedded block is connected to the cassette.The cassette serves as a carrier that can be introduced into acorresponding receptacle of a microtome and fastened there.

The result is an embedded block with cassette in which the sample issecured in stationary fashion. After hardening of the embedding medium,the sample can be sectioned with the microtome into individual thinsample sections that, in a subsequent step, can be stained andinvestigated with a microscope.

EP 2 322 938 B1 discloses an automated machine that is embodied to embedtissue samples onto very special carriers, namely those which aresuitable for being sectioned with a microtome together with the embeddedsample. The machine comprises multiple immovable holders, each holderbeing embodied to hold one of the special carriers during the entireembedding operation. Once a carrier filled with a sample has beenpositioned in a holder, the carrier is filled with an embedding mediumthat is delivered from a dispenser. The carrier is then cooled by theholder, which in order to implement an additional function isadditionally embodied as a cooling unit. During the entire embeddingprocess, each carrier remains in its position defined by the respectiveholder. The dispenser services all of the plurality of holders.

The concept on which this machine is based disadvantageously requires acomplex and malfunction-prone configuration. This relates in particularto the dispenser, which must be able to reach each individual one of theholders so that paraffin heated to above its melting point can bedistributed.

SUMMARY OF THE INVENTION

The object of the present invention is to describe an automatedembedding machine that can be of simpler and less malfunction-proneconfiguration.

The object is achieved by an automated embedding machine that comprisesat least a conveyor, a pouring station, and a cooling station, theconveyor being embodied and arranged to receive casting molds eachhaving at least one histological sample arranged therein, and totransport them to the pouring station which fills each casting mold withan embedding medium heated to above its melting point, and then to thecooling station which cools the embedding medium of each casting mold tobelow its melting point.

A further object of the present invention is to provide a method forembedding histological samples, which method can be carried out insimple and reliable fashion, in particular automatically.

This object is achieved by a method that is characterized by thefollowing steps:

a. inserting histological samples into casting molds, at least onehistological sample being inserted into one casting mold,

b. transferring the casting molds having the samples to a loadingstation of an automated embedding machine that comprises a conveyor, apouring station, and a cooling station,

c. conveying the transferred casting molds, using the conveyor, to apouring station that fills each casting mold with an embedding mediumheated to above its melting point, and

d. conveying the casting molds, filled with the embedding medium, to acooling station that cools the embedding medium of each casting mold tobelow its melting point.

The automated embedding machine according to the present invention hasthe advantage in particular that (in contrast, for example, to theaforementioned machine known from EP 2 322 938 B1) there is no need forthe presence of multiple mutually independent positioning systems,namely on the one hand for the casting molds and on the other hand, forexample, for a dispenser for delivering the embedding medium. Inparticular, only a single conveyor needs to be present, so there is norisk of elements of different transport systems colliding with oneanother, and there is no need to laboriously configure differenttransport systems in such a way that a collision of individual elementsof said systems is avoided.

The automated embedding machine can advantageously comprise at least onefurther station.

A loading station, into which the casting molds each having at least onehistological sample arranged therein are loadable and from which theconveyor receives the casting molds for further transport, can bepresent, for example, as a further station.

Transfer of the casting molds having the samples to a loading station ofan automated embedding machine can be accomplished, for example, in sucha way that individual casting molds are transferred sequentially. It isalso possible, however, for the casting molds to be transferred ingroups. The loading station of the automated embedding machine can beembodied in particular as a loading buffer. This has the advantage thatthere is no need to wait until the previously loaded casting molds havebeen received by the conveyor and transported out of the loading stationbefore further casting molds can be loaded into the loading station.

In the particular embodiment, provision is made that a sorting of theloaded casting molds is performed in the loading buffer. This can occurin particular automatically, for example by way of a control apparatus.The sorting can be accomplished, for example, in such a way that, forexample, casting molds having samples of the same type are sorted intoone group. These can be, for example, samples that are later to bestained in the same manner, or samples that are to be embedded using thesame embedding medium (for example, the same grade of wax), or samplesof the same tissue type. Alternatively or additionally, it is alsopossible to sort with respect to one another the casting molds havingthe samples of a specific patient or of a specific group of patients.

Provision can be made in particular that the casting molds sorted withrespect to one another in a group can be embedded in one treatment cycletogether or in immediately successive treatment cycles. This has theadvantage, for example, that frequent changeovers within the automatedembedding machine are avoided, for example when different samples needto be embedded using different grades of wax and/or at differenttemperatures.

Alternatively or in addition to sorting, a prioritization of individualcasting molds, for example of casting molds having samples to beembedded particularly urgently, can occur in the loading buffer,preferably automatically under the control of a control apparatus. Forexample, a control apparatus can perform a prioritization in such a waythat casting molds having particularly urgent samples are forwarded tothe subsequent stations before casting molds having samples that are noturgent.

Provision can be made, for example, that a reading apparatus in theloading buffer detects, for example on the basis of a code, inparticular a barcode, mounted on the casting mold, the parameters withwhich embedding is to occur, for example the embedding medium with whichthe sample of that casting mold is to be embedded and/or the temperatureat which embedding is to occur and/or the temperature at which coolingis to occur. Provision can also be made for detecting the priority of acasting mold based on such a code.

Alternatively or additionally, other further stations to which thecasting molds are transported by the conveyor can also be present.

In a particular embodiment, the automated embedding machine comprises anunloading station to which the conveyor transports the casting moldshaving the cooled embedding medium. The user, or a further automatedmachine, can remove the completed blocks from the unloading station forfurther processing. It is particularly advantageous if the unloadingstation is embodied as an unloading buffer. This has the advantage ofavoiding formation of a “traffic jam” of completed blocks, which cancause the process of manufacturing further blocks to be halted until thejam has been eliminated. This yields the further advantage that thecompleted blocks do not need to be removed from the automated embeddingmachine immediately after they are manufactured.

In the particular embodiment, provision is made that a sorting of thecasting molds is performed in the unloading buffer. This can beaccomplished in particular automatically, by example under the controlof a control apparatus. The sorting can be accomplished, for example, insuch a way that, for example, casting molds having samples of the samekind are sorted into one group. These can be, for example, samples thatare to be stained in the same manner, or samples that are to besectioned in a microtome in the same manner, or samples of the sametissue type. Alternatively or additionally, it is also possible to sortwith respect to one another in the unloading buffer those casting moldshaving the samples of a specific patient or of a specific group ofpatients, so that they can be removed together.

Alternatively or in addition to sorting, a prioritization of individualcasting molds, for example of casting molds having samples to beembedded particularly urgently, can occur in the unloading buffer,preferably automatically under the control of a control apparatus. Forexample, a control apparatus can perform a prioritization in such a waythat casting molds having particularly urgent samples can be removedfrom the unloading buffer before casting molds having samples that arenot urgent.

Provision can be made, for example, that a reading apparatus in theunloading buffer detects, for example on the basis of a code, inparticular a barcode, mounted on the casting mold, how sorting is tooccur or what priority the respective casting mold has.

An identification station, to which the casting molds are conveyed bythe conveyor in particular immediately after leaving the coolingstation, can be present as a further station. The identification stationcan comprise an identifier that receives and/or reads off a specificcode for each casting mold and/or for the sample present therein and/orfor each block that has been produced. For example, a specific barcodethat the identifier can read off can be imprinted onto each castingmold. Alternatively, a casting mold can also comprise an RFID chip thatpermits identification.

In a very particularly advantageous embodiment, the automated embeddingmachine comprises an information output interface that outputs, forexample to a laboratory information system, an information item about anidentified casting mold and/or an identified sample and/or an identifiedblock. Alternatively or in addition to an information output to alaboratory information system, for example, a report can also beoutputted locally; this can be accomplished, for example, by a printouton paper or by display on a monitor of the automated embedding machine.

The conveyer can be embodied in a very wide variety of ways.

In a particular embodiment the conveyor transports the casting molds ina continuous transport stream along a predefined conveying path. Anembodiment of this kind can advantageously be implemented with verylittle complexity or outlay. In particular, an embodiment in which theconveyor transports the casting molds individually along the predefinedtransport path permits an overall process that is clear and easy tomonitor, and therefore has little susceptibility to malfunction.

The continuous transport stream can proceed in such a way that all thecasting molds always have the same transport speed. An embodiment inwhich the individual casting molds are transported within the continuoustransport stream independently of one another and/or at differentinstantaneous speeds and/or in timed fashion along the predefinedconveying path is, however, particularly advantageous.

Provision can also be made that the conveyor transports the castingmolds in groups along a predefined conveying path. The casting molds ofeach group can, for example be respectively secured in a shared holder.An embodiment of this kind has the advantage of a particularly highthroughput.

In particular, the conveyor can comprise a transport line and/or aconveyor belt. Alternatively or additionally, the conveyor canadvantageously be embodied, for example, as a belt conveyor and/or as asegment conveyor and/or as a roller conveyor and/or as a continuousconveyor.

An embodiment of the automated embedding machine in which the conveyingpath is identical for all casting molds is particularly simple toimplement and particularly unsusceptible to malfunction. It is possible,however, to embody the conveyor in such a way that different castingmolds take different conveyor paths, for example if multiple stations ofone station type are present and are operated in parallel.

In a particular embodiment that can be embodied in particular as analternative to implementation of a continuous transport stream, theconveyor comprises a holder for multiple casting molds which is movablerelative to the stations, the holder being moved by a control apparatusin such a way that each of the casting molds held by the holder travelssuccessively to each of the stations. For example, an X-Y displacementstage with which the holder can be positioned can be present.

In a particular embodiment the sample is cooled exclusively by theaction of cold from one direction, for example from below. This has theadvantage, as compared with cooling from all sides, that stress crackswithin the paraffin do not occur.

In order to ensure that the sample or samples have, within the blockthat is to be produced, a favorable alignment for sectioning with amicrotome and for subsequent microscopic investigation of the sections,provision can advantageously be made that the samples are each alignedrelative to their casting mold in a target position in which the samplesare to be immobilized, and are secured with a securing element in thattarget position during embedding. The automated embedding machine is inthis regard preferably embodied to be used with a casting mold thatcomprises at least one securing element for physically securing a samplein a target position within the casting mold. For example, the samplecan be clamped between the securing element and the bottom of thecasting mold in order to secure the sample in the target position.

The casting mold can be embodied in particular in such a way that it canalso function as a cassette, so that the histological processingoperations that precede embedding, such as fixing and/or infiltration,can be performed on the position sample secured in a target position inthe casting mold. The preceding operations can in particular beaccomplished by a different automated machine.

The securing element can comprise, for example, a clamping means forclamping at least one sample. The clamping means can be embodied, forexample, as a spring-loaded screen.

In order to allow sectioning of the block, once produced, with amicrotome with no risk of damaging the microtome knife on the securingelement, in a very particularly advantageous embodiment the securingelement is removed from the sample during the cooling operation. Thiscan be accomplished in particular by firstly cooling and therebysolidifying the embedding medium, in particular in a locally delimitedmanner within the casting mold, sufficiently that the sample is held inits position by the already solidified parts of the embedding medium,and then removing the securing element from the sample during thefurther cooling process.

An embodiment in which the securing element is removed from the sampleby magnetic force is particularly advantageous, since no additionalmechanical tools that must engage into the casting mold in order toremove the securing element are required. Removal of the securingelement can instead occur in an advantageously noncontact manner,thereby avoiding the risk of damaging the sample or inadvertentlymodifying the orientation of the sample.

The securing element can be embodied as a magnet and/or can containferromagnetic particles. It is also possible, however, for the securingelement to be embodied in at least partially paramagnetic fashion, andfor the cooling station to comprise a preferably controllable magnetwith which a force can be exerted on the securing element.

BRIEF DESCRIPTION OF THE DRAWING FIGURES

The subject matter of the invention is schematically depicted in thedrawings and will be described below with reference to the Figures,identical or identically functioning elements for the most part beingprovided with the same reference characters. In the drawings:

FIG. 1 depicts an exemplifying embodiment of an automated embeddingmachine according to the present invention; and

FIG. 2 depicts another exemplifying embodiment of an automated embeddingmachine according to the present invention.

DETAILED DESCRIPTION OF THE INVENTION

FIG. 1 schematically shows an exemplifying embodiment of an automatedembedding machine according to the present invention that comprises aloading station 1, a pouring station 2, a cooling station 3, anidentification station 4, and an unloading station 5. The automatedembedding machine furthermore comprises a conveyor 6 that is embodiedand arranged to receive casting molds 7 each having at least onehistological sample 8 arranged therein, and to transport them further.

In order to ensure that sample 8 has, within the block to be produced,an alignment that is favorable for further processing, the samples areeach aligned relative to their casting mold 7 in a target position inwhich the samples are to be block-embedded, and are secured in thattarget position with a securing element 12 that can be embodied e.g. asa screen-shaped clamping element. Sample 8 can be clamped in place, forexample, between the clamping element and the bottom of casting mold 7.

Conveyor 6 transports casting molds 7 from loading station 1 firstly topouring station 2, where each casting mold 7 is filled with an embeddingmedium 9, for example paraffin, heated to above its melting point. Theliquid embedding medium 9 is taken from a reservoir container 10 anddelivered in the correct amount, under automatic control, through adispenser nozzle 11 into the respective casting mold 7.

After pouring at pouring station 2, casting molds 7 are transported onby conveyor 6 to cooling station 3, which contains a cooling apparatus13. Here the embedding medium 9 delivered into the individual castingmolds 7 is cooled to below its melting point.

During the cooling operation, the following effect is utilized: in thefirst moments of cooling, the lowest layer of the embedding mediumpresent in casting mold 7 becomes solidified. Because sample 8 abutsdirectly against the bottom of casting mold 7, sample 8 is therebysecured by the solidifying embedding medium 9 in its target position, inwhich it has been held until then by securing element 12.

Because sample 8 is in contact on its upper side with securing element12, which must not be cut into later by the microtome knife, saidsecuring element 12 is then lifted in such a way that a spacing of, forexample, 1 to 2 mm is created between the sample and securing element12. As soon as lifting has occurred, the remaining embedding medium 9 incasting mold 7 can harden.

Lifting is accomplished with the aid of a magnet 14, preferablyautomatically controlled, that exerts a magnetic force on securingelement 12, which can itself be magnetic or can contain magneticparticles. Another possibility for lifting is to lift securing element12 using lever apparatuses or other mechanical means.

After cooling, the casting molds are transported by conveyor 6 fromcooling station 3 to identification station 4, where an identifier 15receives and/or reads off a respective specific code for each castingmold 7 and/or for the sample present therein and/or for each block thathas been produced.

Identifier 15 forwards the information regarding the identified castingmold 7 to an information output interface 16, which is embodied totransmit the information to a laboratory information system and/or to alocal output means, for example to a display screen or a printer.

After the identification operation, casting molds 7 are furthertransported by conveyor 6 to unloading station 5, which is embodied asan unloading buffer. The completed casting molds 7 having the completedblocks can be removed automatically or manually from unloading station5. The hardened blocks are taken out of casting molds 7 for furtherprocessing.

FIG. 2 shows another exemplifying embodiment of an automated embeddingmachine according to the present invention that likewise contains aloading station 1, a pouring station 2, a cooling station 3, anidentification station 4, an unloading station 5, and a conveyor 6.

In this automated embedding machine, conveyor 6 comprises a holder 17for multiple casting molds 7 which is movable relative to stations 2, 3,4, 5, and which is moved by a control apparatus in such a way that eachof the casting molds 7 held by holder 17 travels successively to each ofstations 2, 3, 4, 5. For example, a displacement stage can be presentwith which holder 7 can be displaced in two or three dimensions.

PARTS LIST

-   -   1 Loading station    -   2 Pouring station    -   3 Cooling station    -   4 Identification station    -   5 Unloading station    -   6 Conveyor    -   7 Casting molds    -   8 Sample    -   9 Embedding medium    -   10 Reservoir container    -   11 Dispenser nozzle    -   12 Securing element    -   13 Cooling apparatus    -   14 Magnet    -   15 Identifier    -   16 Information output interface    -   17 Holder

What is claimed is:
 1. A method for embedding histological samples,comprising the steps of: a. inserting histological samples into castingmolds, at least one of the histological samples being inserted into oneof the casting molds, wherein the samples are each aligned relative tothe respective casting mold in a target position in which the samplesare to be block-embedded, and are secured in the target position with asecuring element; b. transferring the casting molds having the samplesto a loading station of an automated embedding machine, the automatedembedding machine further comprising a conveyor, a pouring station, anda cooling station, wherein the loading station is embodied as a loadingbuffer configured to hold a plurality of the casting molds; c. conveyingthe transferred casting molds, using the conveyor, to the pouringstation that fills each of the casting molds with an embedding mediumheated to above a melting point of the embedding medium; and d.conveying the casting molds, filled with the embedding medium, to thecooling station that cools the embedding medium of each of the castingmolds to below the melting point of the embedding medium, wherein thesecuring element is removed from the sample while the embedding mediumis cooled.
 2. The method according to claim 1, wherein the securingelement is removed from the sample by magnetic force.
 3. The methodaccording to claim 1, wherein the automated embedding machine comprisesat least one further station, and the casting molds are transported bythe conveyor to the further station.
 4. The method according to claim 1,wherein the conveyor receives the casting molds for further transportfrom the loading station.
 5. The method according to claim 1, furthercomprising the step of identifying each of the casting molds and/or theat least one sample present therein and/or each solidified block byreading or receiving a specific code associated with the casting moldand/or the at least one sample and/or the solidified block.
 6. Themethod according to claim 5, further comprising the step of outputtingan information item about each of the casting molds and/or the at leastone sample present therein and/or each solidified block to a laboratoryinformation system.
 7. The method according to claim 1, wherein thecasting molds are transported in a continuous transport stream along apredefined conveying path.
 8. The method according to claim 1, whereinthe casting molds are transported individually along a predefinedtransport path.
 9. The method according to claim 1, wherein the castingmolds are transported in groups along a predefined conveying path. 10.The method according to claim 9, wherein the casting molds of each ofthe groups are secured in a shared holder.
 11. The method according toclaim 1, wherein the conveyor comprises a holder for multiple castingmolds, the holder being movable relative to the loading, pouring, andcooling stations by a control apparatus such that each of the castingmolds held by the holder travels successively to each of the loading,pouring, and cooling stations.
 12. The method according to claim 11,wherein the conveying path is identical for all the casting molds. 13.The method according to claim 1, further comprising transporting thecasting molds having the cooled embedding medium by the conveyor to anunloading station of the automated embedding machine, wherein theunloading station is embodied as an unloading buffer configured to holda plurality of the casting molds.